PROJECT SUMMARY The mission of our VA Rehabilitation Research and Development Center for Limb Loss Prevention and Prosthetic Engineering is to improve the quality of life and functional status of veterans who are at risk for, or have undergone, a lower extremity amputation. The Center brings together investigative teams that identify clinical problems, model them into hypothesis-driven research, conduct experiments, and make evidence- based conclusions before disseminating the results to veteran, clinical, and scientific audiences. Our Center includes three major cores: (1) Limb Loss Prevention, (2) Prosthetic Engineering, and (3) Rehabilitation Outcomes. The Limb Loss Prevention core aims to reduce functional and anatomical limb loss by studying the disease processes that lead to aberrant limb function and by developing novel, state-of-the-art technologies for studying the foot. Highly specialized techniques, such as biplane fluoroscopy, cadaveric gait simulation, gated MRI loading, and computational modeling, will be employed to quantify the effects of foot deformity, ankle arthritis and diabetes, and to compare the effect of different treatment options. The Prosthetic Engineering core aims are to enhance mobility, reduce the risk of injury, and improve the comfort of veteran amputees. We address these needs by designing and evaluating novel state-of-the-art prostheses that leverage advances in robotics, computation, and instrumentation. The Rehabilitation Outcomes core integrates the complex multi-dimensional issues of medical co-morbidity, psychological status, and social factors and their impact on amputee functional outcome. The development and evaluation of group-based therapeutic interventions, and the improvement of the amputation level decision making process are the foci of this core. Since our last Center renewal in 2012, we have been awarded $5.4M in intramural funding via 15 VA RR&D grants and $3.3M in extramural funding via 6 non-VA federal grants. During the same fiscal period (2013- 2015), the Center has published 69 peer-reviewed articles, 5 book chapters, 3 conference papers, 67 conference abstracts, and our investigators have given 108 presentations and invited lectures. We have also expanded our research capabilities through many successful collaborations with multiple departments at the University of Washington, other top-tier research Universities, leading research institutions, VAPSHCS Health Services, and ERIC (Epidemiology Research an Informatics Center) investigators, as well as clinician/scientists at other VA Medical Centers. Our current 6,300 square feet of laboratory and office space will nearly double, and be transformed into state-of-the-art research facilities when we transition into the new Mental Health and Research Building in 2017. Our Center includes a group of highly productive and recognized senior investigators including two who have won the prestigious Paul B. Magnuson Award for Rehabilitation Research and two recipients of VA Research Career Scientist awards. We have also recruited three early-career PhD researchers and two Career Development Award winners who bring important skillsets to further advance the Center mission. Our Center investigative team includes clinician/scientists with expertise in Orthopaedics, Rehabilitation Medicine, and Rehabilitation Psychology. This strong clinical linkage ensures that our research is relevant to the veteran patients who are the focus of our work. We have developed an impressive training program to create a new generation of scientists who will contribute to veteran care including: undergraduate, graduate and medical students, post-doctoral fellows, interns/residents, and clinical fellows. Our Center?s work is further enhanced by a skilled research team including: MS engineers, research assistants, a biostatistician, and a prosthetist. In summary, this Center has developed a remarkable infrastructure that has enabled it to conduct both high quality, and highly prolific research that is responsive to the emerging needs of our veterans.